Are isocitrate lyase and phosphoenolpyruvate carboxykinase involved in gluconeogenesis during senescence of barley leaves and cucumber cotyledons?

The aim of this study was to investigate whether gluconeogenesis catalysed by phosphoenolpyruvate carboxykinase (PEPCK) occurs during leaf senescence. This was addressed by determining changes in the abundance and intercellular location of enzymes necessary for gluconeogenesis during the senescence of barley leaves and cucumber cotyledons. PEPCK was never present in barley leaves, despite the presence of large amounts of isocitrate lyase (ICL), a key enzyme of the glyoxylate cycle, and of its product, glyoxylate. Although PEPCK was present in non-senescent cucumber cotyledons, its abundance declined during senescence. Throughout senescence, PEPCK was only present in the trichomes and vasculature, whereas ICL was located in mesophyll cells. Pyruvate,Pi dikinase (PPDK) which, in concert with NAD(P)-malic enzyme, is also capable of catalysing gluconeogenesis, was present in non-senescent barley leaves and cucumber cotyledons, but in both plants its abundance decreased greatly during senescence. The abundance of ICL was greatly reduced in senescing detached barley leaves by either illumination or by co-incubation with sucrose, and greatly increased in darkened attached barley leaves. These results argue against the large-scale occurrence of gluconeogenesis during senescence catalysed either by PEPCK or PPDK. In cucumber cotyledons, PEPCK may play a role in metabolic processes linked to the export of amino acids, a role in which phosphoenolpyruvate carboxylase may also be involved. The amount of ICL was increased by starvation and during senescence may function in the conversion of lipids to organic acids, which are then utilised in the mobilisation of amino acids from leaf protein.

Care in the community--elderly people living alone at home.

A study carried out in East Anglia identified a number of aspects of the lives of elderly people living alone and some of these are reported here. A sample of 2000 elderly people from 20 general practitioner practices was selected for interview. Overall, there was a response rate of 88 per cent. Of those age 75 and over, 43 per cent lived alone, this proportion being higher in urban areas, in council, privately rented and sheltered housing and amongst women. There is a high level of informal support for elderly people living alone, although there is also a large number who do not have regular frequent visitors. Of the statutory services, home helps visit nearly a quarter of those aged 75 and over living alone, on a weekly basis. In terms of at least one activity of daily living, shopping, those living alone exhibit a higher level of independence than those living with others, but nearly a quarter of those aged 75 and over living alone do rely on someone else entirely to do their shopping for them. The study identified a number of aspects of ill health in elderly people. There was a substantial proportion with urinary incontinence and, amongst those aged 75 and over living with others, a significant proportion with a degree of faecal incontinence. There was also a high proportion of people unable to cut their own toenails.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental DNA-binding and computer modelling studies on an analogue of the anti-tumor drug amsacrine.

The DNA-binding properties of the anti-cancer drug amsacrine and a 9-aminoacridine analogue substituted at the 4 position with a 4-methanesulphonanilido-group, have been examined by means of unwinding, melting and equilibrium binding experiments. These find that the latter compound is at least as effective as a DNA-binder and intercalator as amsacrine itself. Molecular modelling and energetic calculations have confirmed this, and have produced plausible intercalation geometries. These show that there are subtle differences in the low-energy minor groove arrangements adopted by the substituents of the two drugs. Speculation is advanced that these differences may be relevant to the marked differences in cytotoxicity shown by the two compounds.

Study of trainer/trainee workload with special reference to the care of the elderly.

A study of the workload of trainers and their trainees in general practice, was undertaken throughout East Anglia. Thirty trainer/trainee pairs returned data over a two-week period and follow-up information was obtained from five pairs, eight months later. A simple encounter form was used.Trainee workloads were found to be similar to those of earlier studies, though there was considerable variation between the workloads. Trainees had little experience with elderly patients, and there was a lack of teamwork between members of the practices in providing care for the elderly.

The metabolism of some 1-hydroxylated indoles in the rat.

A number of N-hydroxylated indole derivatives have been fed to rats and the urinary metabolites compared with those obtained on feeding the corresponding N-H indoles. 1-Methoxy- and 1-acetoxy-indole were metabolized to compounds normally observed on feeding indole. 1-Hydroxy- and 1-methoxy-indole-3-carboxylic acids were both partially excreted unchanged and reduced to indole-3-carboxylic acid which was excreted along with its glucuronide. Indole-3-glyoxylic acid and its 1-methoxy derivative were excreted almost entirely unchanged. 1-Hydroxyindole-3-glyoxylic acid was mostly excreted unchanged, but some reduction to indole-3-glyoxylic acid took place. The stability of these acids is associated with their low pKa values. The significance of the removal in vivo of groups attached through oxygen to the 1 position of indoles in relation to the synthesis of new potential medicinal agents is noted.

Heberden Oration 1981: epidemiology and the arthritides.

The multifactorial control of serum uric acid levels is discussed from an epidemiological point of view and the principles at issue related to the epidemiology of osteoarthrosis. It is shown that in osteoarthrosis the clinical characteristics vary from one joint group to another. Association of x-ray changes with pain varies between joints and between sexes for the various joints. The disease tends to be commoner in females but not in all age groups. There is an association between obesity and osteoarthrosis in the hands and knees but not the hips or ankles. These differences raise questions about the homogeneity of generalised osteoarthrosis. Such questions might be answered by epidemiological studies which consider individual joint groups and are carefully directed towards specific hypotheses, the development of which could be facilitated by the use of iconic models.

Acidic epinephrine analogues derived from 1H, 3H-2,1,3-benzothiadiazole 2,2-dioxide and from trifluoromethanesulfonanilide. A new synthesis of 1H,3H-2,1,3-benzothiadiazole 2,2-dioxide.

Treatment of N,N'-dibenzyl-1,2-diaminobenzene (2) successively with thionyl chloride and then m-chloroperbenzoic acid gave N,N'-dibenzyl-1H,3H-2,1,3-benzothiadiazole 2,2-dioxide (4), which gave (via routes analogous to standard epinephrine syntheses) four bicyclic catecholamine analogues 7a-d. Hydrogenolysis of 4 yielded the parent heterocycle 5 in the first practicable synthesis avoiding expensive sulfamide (Scheme I). The trifluoromethanesulfonamidoacetophenones 8m and 8p on similar elaboration gave triflanilide catecholamine analogues 14m, 14p,17m, and 17p (Scheme II). 4,4'Dimethoxybenzhydrylamine (15) is recommended for the regiospecific synthesis of primary amines from epoxides (Scheme II). Series 7,14, and 17 were inactive in animal cardiovascular screens. Selected compounds were also screened in bronchodilator and in in vitro dopamine-, clonidine-, and prazosin-receptor binding assays as appropriate; again no activity was observed. Steric lipophilicity, and acidity factors are discussed, and the inactivity is ascribed to the high acidity of both systems (pKa approximately equal to 4).

Effects of ring substituents and linker chains on the bifunctional intercalation of diacridines into deoxyribonucleic acid.

Sedimentation experiments with closed circular duplex PM2 deoxyribonucleic acid (DNA) and viscosity measurements with sonicated rodlike DNA fragments have been performed to investigate unwinding and extension of the DNA helix associated with binding of homologous series of diacridines. When the acridine nuclei are linked via 9-amino substituents with chains permitting interchromophore separation in the critical region between 8.8 and 11.3 A, it is found that substituents at positions 2, 3, and 6 restrict bifunctional intercalation to compounds capable of sandwiching at least two base pairs in the intercalated complex. Unsubstituted diacridines, and derivatives bearing an ethyl group at position 4, can bis-intercalate with a significantly shorter linking chain. The presence of amino groups in the linker does not affect the ability to bis-intercalate but increases the helix unwinding angle by 30--40% and decreases the helix extension per bound ligand molecule by 11--18%. Bifunctional reaction is observed with a diacridine linked via the 4--4' positions showing that 9-aminoacridine can intercalate in at least two major orientations with the 9 or 10 position directed toward the helix axis. Both orientations can be accommodated simultaneously within a single diacridine linked via the 9--4' positions with a bridge sufficiently long to encompass two base pairs. An acridone substituted at positions 4 and 5 with positively charged side chains intercalates with a helix unwinding angle indistinguishable from that of ethidium whereas an uncharged bisacridone failed to yield a detectable complex with DNA. Tilorone dihydrochloride, a structurally similar antiviral drug, was found to intercalate with an unwinding angle approximately half that of ethidium. The potentially bifunctional bisquinoline drug dequalinium causes relaxation of the supercoiling of PM2 DNA but probably not by simultaneous intercalation of both its chromophores.

Teachers in general practice: a comparative study.

Thirty-nine randomly selected general practitioners in the Cambridgeshire Health Area were surveyed in an attempt to determine whether there were prior differences between those practitioners who choose to become involved with undergraduate medical students and those who choose not to. Teachers were found to have graduated more recently, subscribe to more journals and were more likely to use medical libraries than non-teachers. All the solo practitioners in the study and two of the four practitioners in two-man groups belonged to a subgroup of non-teachers who had never had students and did not want students in the future. This subfroup also subscribed to fewer journals than the other groups, bought fewer textbooks and used medical libraries less. The only prior differences between teachers and non-teacher that have been demonstrated are year of graduation and type of practice. Other differences could well be attributed to the influence of the students themselves. Studies are needed to clarify this issue, especially as it realates to continuing medical education.